Aflibercept With or Without Suprachoroidal CLS-TA for Diabetic Macular Edema: A Randomized, Double-Masked, Parallel-Design, Controlled Study.

Purpose This study evaluated the potential safety, efficacy, and durability advantages of CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept compared to aflibercept monotherapy for the treatment of Diabetic Macular Edema (DME). Design TYBEE was a prospective, randomized, controlled, double-masked study. Subjects were randomized 1:1 to CLS-TA in conjunction with aflibercept (‘Active’) or aflibercept monotherapy (‘Control’) and tracked over 24 weeks. Participants Treatment-naive DME subjects with Best Corrected Visual Acuity (BCVA) 20-70 letters and central subfield retinal thickness (CST) > 300 μm. Methods Subjects in the Active group (n=36) received CLS-TA in conjunction with aflibercept at baseline and week 12. Subjects in the Control group (n=35) received aflibercept at baseline, week 4, week 8, and week 12. All subjects were eligible to receive aflibercept as needed (PRN) at weeks 4, 8, 16 and 20 per additional therapy criteria: presence of macular edema CST ≥ 340 μm; increase in CST of > 50 μm associated with a decrease in BCVA (≥6 letters from the previous visit or 10 letters from the best measurement) Main Outcome Measure Mean change in BCVA from baseline; treatment differences were assessed with a 2-sided significance level of 0.10. Results Mean changes from baseline in BCVA at week 24 were not statistically different in the Active and Control groups (+11.4 and +13.8 letters, p=0.288, intention to treat (ITT); +12.3 and +13.5 letters, p=0.664, per protocol (PP) populations, respectively). Greater improvement in CST was seen in the Active group versus Control (-212.1 μm and -178.6 μm, p=0.089, ITT; -226.5 μm and -176.1 μm, p=0.035, PP, respectively). Eyes in the Active group received an average of 2.6 treatments, while eyes in the Control group received an average of 4.6 treatments. No treatment-related serious AEs were observed. Elevated IOP and cataract events trended higher in the Active group versus the Control group. Conclusion CLS-TA administered suprachoroidally in conjunction with IVT aflibercept in the treatment of DME provides no visual benefit at 24 weeks follow up compared to IVT aflibercept monotherapy, but a modest anatomical benefit and the potential to reduce treatment burden. Ocular adverse events were low for both arms.